Study of the contribution of ectopic kainate receptors in the network dynamics of the epileptic dentate gyrus
Team “Neuronal coding and plasticity in epilepsy”
Temporal lobe epilepsy is one of the most common forms of epilepsy in adults. The epileptic hippocampus undergoes significant reorganisation of neuronal circuits such as neuronal degeneration and the formation of new aberrant connections between surviving neurons. Particularly in the dentate gyrus, granule cells form a recurrent excitatory network by sprouting their axon, the mossy fibre.This pathological network facilitates the onset of epileptic seizures and abnormal epileptiform events. These aberrant connections operate significantly via ectopic kainate receptors in addition to AMPA receptors. These receptors enhance the excitability of granule cells and play a pivotal role in the onset of epileptiform discharges and chronic epileptic seizures in temporal lobe epilepsy.
The aim of my thesis was to better understand the mecanisms by which kainate receptors modulate network dynamics and contribute to the generation of epileptiform activity in the dentate gyrus. To this end, I used two complementary methods.
A first in vitro study to assess the role of kainate receptors within the micro-structure of epileptiform discharges.
The second in silico study consists in modeling the epileptic dentate gyrus with kainate receptors. Their specific impact on network is assessed by simulations.
My two studies highlight that kainate receptors influence the pathological recruitment of neurons in epileptiform activity. While AMPA receptors primarily drive pathological activity, kainate receptors act as important modulators of abnormal neuronal recruitment. Consequently, my findings suggest a binary mechanism, with a threshold for the onset of epileptiform discharges and kainate receptors contributing to cross it.
Christophe Mulle, Rapporteur – IINS – Ecole des Neurosciences de Bordeaux
Bruno Delord, Rapporteur – ISIR, Paris
Delphine Salort, Présidente – Institut de Biologie Paris Seine
Dominique Debanne, Examinateur – UNIS, Marseille
Charles Quairiaux, Examinateur – UNIGE,Genève
Thomas Marissal, Co-directeur de thèse – Inmed, Marseille
Valérie Crépel, Directrice de thèse – Inmed Marseille
Friday 1st December 2023 at 2pm – Inmed conference room